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The effect of HLA-B allele on the IDDM risk defined by DRB1*04 subtypes and DQB1*0302.

https://arctichealth.org/en/permalink/ahliterature207373
Source
Diabetes. 1997 Nov;46(11):1888-92
Publication Type
Article
Date
Nov-1997
Author
S. Nejentsev
H. Reijonen
B. Adojaan
L. Kovalchuk
A. Sochnevs
E I Schwartz
H K Akerblom
J. Ilonen
Author Affiliation
Turku Immunology Centre and Department of Virology, University of Turku, Finland.
Source
Diabetes. 1997 Nov;46(11):1888-92
Date
Nov-1997
Language
English
Publication Type
Article
Keywords
Alleles
Diabetes Mellitus, Type 1 - epidemiology - genetics - immunology
Dimerization
Estonia
Ethnic Groups - genetics
Gene Frequency
Genetic markers
HLA-B Antigens - genetics
HLA-DQ Antigens - genetics
HLA-DQ beta-Chains
HLA-DR Antigens - genetics
HLA-DRB1 Chains
Humans
Latvia
Reference Values
Risk factors
Russia
Abstract
The genes encoding the HLA-DQ heterodimer molecules, DQB1 and DQA1, have been found to have the strongest association with IDDM risk, although there is cumulative evidence for the effect of other gene loci within the major histocompatibility complex gene region. After the HLA-DQ locus, the HLA-DR locus has been suggested most often as contributing to the disease susceptibility. In this study we analyzed at the population level the effect of DR4 subtypes and class I, HLA-B alleles, on IDDM risk when the influence of the DQ locus was stratified. In all three populations studied (Estonian, Latvian, and Russian), DQB1*0302 haplotypes most frequently carried DRB1*0401 or DRB1*0404. DRB1*0401 was the most prevalent subtype in IDDM patients, whereas DRB1*0404 was decreased in frequency. DRB1*0402 was also prevalent among Russian haplotypes, but was not associated with IDDM risk. When HLA-B alleles were analyzed, strong associations between the presence of specific B alleles and DRB1*04 subtypes were detected. The HLA-B39 allele was found significantly more often in DRB1*0404-DQB1*0302-positive patients than in healthy control subjects positive for this haplotype: 27 of 54 (50%) vs. 4 of 49 (8.2%) (P
PubMed ID
9356041 View in PubMed
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HLA-DR4 subtype and -B alleles in DQB1*0302-positive haplotypes associated with IDDM. The Childhood Diabetes in Finland Study Group.

https://arctichealth.org/en/permalink/ahliterature206798
Source
Eur J Immunogenet. 1997 Oct;24(5):357-63
Publication Type
Article
Date
Oct-1997
Author
H. Reijonen
S. Nejentsev
J. Tuokko
S. Koskinen
E. Tuomilehto-Wolf
H K Akerblom
J. Ilonen
Author Affiliation
Turku Immunology Centre, University of Turku, Finland.
Source
Eur J Immunogenet. 1997 Oct;24(5):357-63
Date
Oct-1997
Language
English
Publication Type
Article
Keywords
Adolescent
Alleles
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology - genetics - immunology
Disease Susceptibility
Finland - epidemiology
Gene Frequency
Genetic Linkage
HLA-B Antigens - analysis - genetics
HLA-DQ Antigens - genetics
HLA-DQ beta-Chains
HLA-DR Antigens - analysis - genetics
HLA-DR4 Antigen - analysis - genetics
HLA-DRB1 Chains
Haplotypes - genetics
Humans
Risk factors
Abstract
We determined the distribution of DR4 subtypes in 309 DQB1*0302-positive haplotypes found in insulin-dependent diabetes mellitus (IDDM) patients and 70 control haplotypes present only in healthy family members. An increased frequency of DRB1*0401 allele (74.4% vs. 55.7%, P = 0.003) and a decrease of DRB1*0404 allele (23.6% vs. 40.0%, P = 0.0064) was revealed. A further analysis of extended haplotypes demonstrated strong linkages between various B alleles and DRB1*04 subtypes. HLA-B39 was more frequent in DRB1*0404-DQB1*0302-positive IDDM haplotypes compared with control ones (37.0% vs. 14.3%, P = 0.049), suggesting an involvement of the region telomeric to HLA-DRB1 in the susceptibility to IDDM.
PubMed ID
9442803 View in PubMed
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HLA haplotype analysis in Finnish patients with rheumatoid arthritis.

https://arctichealth.org/en/permalink/ahliterature195543
Source
Arthritis Rheum. 2001 Feb;44(2):315-22
Publication Type
Article
Date
Feb-2001
Author
J. Tuokko
S. Nejentsev
R. Luukkainen
A. Toivanen
J. Ilonen
Author Affiliation
Department of Medical Microbiology, University of Turku, Finland.
Source
Arthritis Rheum. 2001 Feb;44(2):315-22
Date
Feb-2001
Language
English
Publication Type
Article
Keywords
Arthritis, Rheumatoid - epidemiology - genetics
Child
Family Health
Female
Finland - epidemiology
HLA-DP Antigens - genetics
HLA-DR Antigens - genetics
HLA-DRB1 Chains
Haplotypes
Humans
Microsatellite Repeats - genetics
Abstract
To further characterize the HLA gene products that play an important role in the pathogenesis of rheumatoid arthritis (RA).
One hundred thirty-four haplotypes from 67 Finnish RA patients and 77 control haplotypes were analyzed for HLA-DRB1 loci, associated alleles of the HLA-DQB1 locus, alleles of the type 2 transporter-associated antigen processing (TAP2) genes, and HLA-B27. In addition, a panel of microsatellite markers within the HLA class I and class III regions was studied.
The frequency of HLA-DRB1*04 in the haplotypes of RA patients was found to be 34% (45 of 134) compared with 14% (10 of 72) in control haplotypes (P = 0.004). The frequency of HLA-DRB1*13 was decreased in RA haplotypes (4%, or 5 of 134) in contrast to control haplotypes (24%, or 17 of 72) (P = 0.000031). The decrease in DRB1*13 was not secondary to the increase in DRB1*04, since it was also found among DRB1*04-negative haplotypes (P
PubMed ID
11229461 View in PubMed
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Intercellular adhesion molecule-1 (ICAM-1) K469E polymorphism: no association with type 1 diabetes among Finns.

https://arctichealth.org/en/permalink/ahliterature197848
Source
Tissue Antigens. 2000 Jun;55(6):568-70
Publication Type
Article
Date
Jun-2000
Author
S. Nejentsev
A P Laine
O. Simell
J. Ilonen
Author Affiliation
JDF Centre for Prevention of Type 1 Diabetes in Finland, Turku. serneje@utu.fi
Source
Tissue Antigens. 2000 Jun;55(6):568-70
Date
Jun-2000
Language
English
Publication Type
Article
Keywords
Adolescent
Alleles
Child
Child, Preschool
Diabetes Mellitus, Type 1 - epidemiology - genetics
Female
Finland - epidemiology
Gene Frequency
Glutamic Acid - genetics
Humans
Infant
Infant, Newborn
Intercellular Adhesion Molecule-1 - genetics
Lysine - genetics
Male
Polymorphism, Genetic - genetics
Abstract
The intercellular adhesion molecule-1 (ICAM-1) has an important role in the process of lymphocyte migration and activation, and is supposed to be involved in the pathogenesis of type 1 diabetes. We studied A/G (K469E) polymorphism of the ICAM-1 gene in 218 type 1 diabetes patients and 212 controls from Finland and found no association. We then studied transmission of the ICAM-1 alleles in 102 Finnish families using a transmission disequilibrium test (TDT). Alleles A and G were transmitted to the affected offspring in 50% each. Stratification by the HLA-DQB1-DQA1 genotypes, sex and age at onset did not reveal association. Our data demonstrate that in the Finnish population K469E polymorphism of the ICAM-1 gene is not associated with type 1 diabetes.
PubMed ID
10902613 View in PubMed
Less detail

Population-based genetic screening for the estimation of Type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci.

https://arctichealth.org/en/permalink/ahliterature199628
Source
Diabet Med. 1999 Dec;16(12):985-92
Publication Type
Article
Date
Dec-1999
Author
S. Nejentsev
M. Sjöroos
T. Soukka
M. Knip
O. Simell
T. Lövgren
J. Ilonen
Author Affiliation
Turku Immunology Centre and Department of Virology, University of Turku, Finland. serneje@utu.fi
Source
Diabet Med. 1999 Dec;16(12):985-92
Date
Dec-1999
Language
English
Publication Type
Article
Keywords
Biological Markers
Child
Cohort Studies
DNA Probes
Diabetes Mellitus, Type 1 - genetics
Finland
Genetic Testing
Genotype
HLA-DQ Antigens - genetics
HLA-DQ alpha-Chains
HLA-DQ beta-Chains
HLA-DR Antigens - genetics
HLA-DRB1 Chains
Humans
Infant, Newborn
Nucleic Acid Hybridization
Polymerase Chain Reaction
Prospective Studies
Risk factors
Sensitivity and specificity
Abstract
To improve sensitivity and specificity of the diabetes risk assessment of the population-based genetic screening used in the Finnish Diabetes Prediction and Prevention (DIPP) trial.
One thousand consecutive newborns enrolled in the DIPP were compared with 316 samples from children with Type 1 diabetes mellitus. A modification of the previously described technique based on hybridization of relevant PCR products with five lanthanide-labelled probes detected by time-resolved fluorometry (TRF) was used. A new probe was designed and allowed discrimination between DQB1*0602 and 0603 alleles, in addition to DQB1*02, *0301 or *0302, each of which required specific probes. A new, added screening strategy was developed for individuals carrying low-risk genotypes through specific typing of DQA1 *05 and *0201 alleles in DQB1*02 positive, and DRB1 typing for DR4 subtypes in DQB1*0302 positive subjects, with a new specifically designed high-resolution TRF-based DR4 subtyping technique.
This two-step screening approach enhanced the sensitivity of the detection of genetic risk for Type 1 diabetes mellitus in this cohort up to 85.4%. In the general population cohort, 24.4% were identified for prospective follow-up, 2.6% of these are expected to develop Type 1 diabetes mellitus before the age of 15 years. Exclusive typing for HLA-DQB1 locus as an alternative screening strategy had sensitivities of 26.3-77.2% with general population cohorts of 2.3-23.1% identified for follow-up.
The described strategy for genetic prediction of Type 1 diabetes mellitus relies on the convenient genotyping procedure and could be applied in large scale screening projects such as DIPP.
PubMed ID
10656226 View in PubMed
Less detail